TY - JOUR

T1 - The pathobiology of thrombosis, microvascular disease, and hemorrhage in the myeloproliferative neoplasms

AU - Hasselbalch, Hans Carl

AU - Elvers, Margitta

AU - Schafer, Andrew I.

N1 - Publisher Copyright: © 2021 American Society of Hematology

PY - 2021

Y1 - 2021

N2 - Thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality in the Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). In these disorders, circulating red cells, leukocytes, and platelets, as well as some vascular endothelial cells, each have abnormalities that are cell-intrinsic to the MPN driver mutations they harbor (eg, JAK2 V617F). When these cells are activated in the MPNs, their interactions with each other create a highly proadhesive and prothrombotic milieu in the circulation that predisposes patients with MPN to venous, arterial, and microvascular thrombosis and occlusive disease. Bleeding problems in the MPNs are caused by the MPN blood cell-initiated development of acquired von Willebrand disease. The inflammatory state created by MPN stem cells in their microenvironment extends systemically to amplify the clinical thrombotic tendency and, at the same time, preferentially promote further MPN stem cell clonal expansion, thereby generating a vicious cycle that favors a prothrombotic state in these diseases.

AB - Thrombotic, vascular, and bleeding complications are the most common causes of morbidity and mortality in the Philadelphia chromosome–negative myeloproliferative neoplasms (MPNs). In these disorders, circulating red cells, leukocytes, and platelets, as well as some vascular endothelial cells, each have abnormalities that are cell-intrinsic to the MPN driver mutations they harbor (eg, JAK2 V617F). When these cells are activated in the MPNs, their interactions with each other create a highly proadhesive and prothrombotic milieu in the circulation that predisposes patients with MPN to venous, arterial, and microvascular thrombosis and occlusive disease. Bleeding problems in the MPNs are caused by the MPN blood cell-initiated development of acquired von Willebrand disease. The inflammatory state created by MPN stem cells in their microenvironment extends systemically to amplify the clinical thrombotic tendency and, at the same time, preferentially promote further MPN stem cell clonal expansion, thereby generating a vicious cycle that favors a prothrombotic state in these diseases.

U2 - 10.1182/blood.2020008109

DO - 10.1182/blood.2020008109

M3 - Review

C2 - 33649757

AN - SCOPUS:85104625509

VL - 137

SP - 2152

EP - 2160

JO - Blood

JF - Blood

SN - 0006-4971

IS - 16

ER -